Large-Scale Non-Invasive Imaging of C. elegans

Introduction

Presentation by Fred from Magnitude Biosciences, a C. elegans CRO based in the UK and a spin-out from Durham University.
Key contributors: David (CEO), Chris (CTO), and Fred (presenter).

Lifespan assays are common experiments in worm research.
Process: Culture C. elegans on petri dishes (some untreated as controls, others treated with chemicals or mutations).
- Worms are incubated and observed under a microscope for movement to determine if alive.
Challenges:
- Requires skill and may vary with operator experience.
- Time-consuming (counting many worms across multiple plates).
- Use of arbitrary time points for observations, leading to potential inaccuracies.
- Disruptive manipulations (light, temperature, mechanical) can affect worms.
- Data obtained is primarily qualitative (alive/dead) with limited quantitative insights.

Develop a method that is:
- Quantitative and less biased.
- More reproducible and reliable.

Solution: Automated image acquisition and data processing.
- Chris's expertise in physics and optics complements David's background in biology and aging.
Benefits:
- High reproducibility through standardized data acquisition and processing.
- Non-invasive: worms remain in a stable environment throughout the experiment.
- Continuous monitoring minimizes disruptions.
Experimental Setup:
- 15-20 plates at a time, imaging up to 50 worms per plate.
- Optimal conditions maintained (24 degrees for SS104 strain).
- Continuous data capture (image every 0.8 seconds for 160 seconds, repeated every 5 minutes).

Data Granularity: Adjusted based on experimental needs, focusing on the early adult stage (larval stage 4 to 14 days).
Preparation Consistency: Utilizes defined amino acid medium to avoid batch variation, along with strict schedules for culture preparations.

Enhanced data representation for behavior and mobility of C. elegans.
- Case Study: Comparison between control strain AM134 and Alzheimer model GMC101.
  - Observed a decline in movement over time, more pronounced in GMC101.
- Effect of Chemical Treatment (SMX):
  - Dose-response observed with increased lifespan, illustrated by shifting movement curves.
  - Highlights trade-offs between early and later activity in worms.
Speed & Behavior Monitoring:
- Analyzed speed and the fraction of worms moving at specific thresholds, allowing deeper insights into activity and mobility.
- Explored exploratory behaviors and chemotaxis without manual disruption.

Automation enhances data quality and throughput in lifespan experiments.
Provides opportunities for mining extensive data across various behavioral and physiological parameters.
Contact information provided for further inquiries and access to detailed resources.